A penalty from Alexander Samedov set the ball rolling for Lokomotiv, and second-half strikes from Maicon and Dame N'Doye were enough to see them back in control of the title race - which comes with an automatic UEFA Champions League place.
Volga remain second-bottom after their seventh loss in a row, with the club winless since October and deep in relegation danger.
On Sunday, a second-half hat-trick from Venezuela striker Jose Rondon helped Zenit leapfrog Lokomotiv to the summit for just 24 hours, as they hammered Rubin Kazan 6-2.
Making Rondon's efforts more remarkable was the fact he was a second-half substitute.
The 24-year-old - who moved from Rubin in January - was introduced in the 66th minute but still had time to net a treble, with Hulk also scoring two penalties for the victors.
The Brazilian striker struck twice from the spot to put Zenit into a 2-0 lead within 35 minutes, and although Sardar Azmoun reduced the arrears for the visitors, Rondon took control of the game as Andre Villas-Boas' men ran out comfortable winners.
CSKA Moscow continued their impressive run of form, with a 3-1 win at Krylya Sovetov giving them their fourth successive league win. They sit third and remain in the title race, five points behind Lokomotiv.
Serbia midfielder Zoran Tosic scored twice, and Seydou Doumbia - the league's joint top scorer with 14 - added the other as Alan Chochiev's late consolation meant little for Krylya.
Bottom-placed Anzhi shocked Champions League-chasing Dinamo Moscow 4-0 - Alexander Burharov, Fedor Smolov, Serder Serderov and Makhach Gadzhiev scoring for the hosts.
It may be too little too late for Anzhi, who have won just two league games this season, and they remain five points adrift of the relegation play-off places.
Terek Grozny's fourth win in five matches moved them within two points of safety, with Oleg Ivanov's goal helping them to a 1-0 triumph at Amkar Perm.
Other results saw Kuban Krasnodar beat Tom Tomsk 2-0, while Rostov beat Krasnodar by the same scoreline and Spartak Moscow suffered a shock 1-0 home loss to the resurgent Ural.
